This project focuses on basic and applied research on human retroviruses, HIV-1 and HTLV-I. It covers three broad areas: I) basic research studying the regulated expression of HIV-1; II) basic research on cellular transformation events as related to HTLV-I; and III) applied research towards developing small molecular inhibitors targeted against HIV-1. Some notable scientific advances from our research program in 2002-2003 include: 1) the finding that human cyclin T1 has a transcriptional activation domain and can be recruited to the HIV-1 LTR by Sp1; 2) the characterization of small Tat pepetides which can be used to inhibit HIV-1 replication; 3) the identification of a small molecule which binds avidly to TAR RNA and which can inhibit HIV-1 replication; 4) the demonstration that the second exon of Tat contains an in vivo replication important function; 5) the finding that Tat is ubiquinated and that ubiquination of Tat does not dictate proteolysi; 6) the elucidation of different requirements for p300 and PCAF in the activation of integrated versus non-integrated HTLV-I LTR; and 7) the unexpected discovery that Tax can repress telomerase expression in human cells.